Immunotherapy‐induced sarcoidosis in patients with melanoma treated with PD‐1 checkpoint inhibitors: Case series and immunophenotypic analysis

• Published in: International journal of rheumatic diseases Vol. 20; no. 9; pp. 1277 - 1285
• Main Authors: Lomax, Anna J., McGuire, Helen M., McNeil, Catriona, Choi, Clara J., Hersey, Peter, Karikios, Deme, Shannon, Kerwin, Hal, Sebastian, Carr, Urszula, Crotty, Anne, Gupta, Sandeep K., Hollingsworth, Jane, Kim, Haewon, Fazekas de St Groth, Barbara, McGill, Neil
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.09.2017
• Subjects: Adrenal Cortex Hormones - therapeutic use; Adult; Aged; Antibodies; Antineoplastic Agents, Immunological - adverse effects; Apoptosis; Biomarkers - blood; Biopsy; CCR6 protein; Cell death; Chemokine receptors; CXCR3 protein; Cytometry; Female; Helper cells; Humans; Immune checkpoint; Immunophenotyping; Immunotherapy; Immunotherapy - adverse effects; Leukocytes (mononuclear); Lymphocytes T; Male; Melanoma; Melanoma - blood; Melanoma - drug therapy; Melanoma - immunology; Melanoma - secondary; Metastases; Middle Aged; Neoplasm Staging; nivolumab; PD-1 protein; pembrolizumab; Peripheral blood mononuclear cells; Phenotype; Positron-Emission Tomography; Predictive Value of Tests; programmed cell death 1; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - immunology; Sarcoidosis; Sarcoidosis, Pulmonary - blood; Sarcoidosis, Pulmonary - chemically induced; Sarcoidosis, Pulmonary - diagnosis; Sarcoidosis, Pulmonary - drug therapy; Skin Neoplasms - blood; Skin Neoplasms - drug therapy; Skin Neoplasms - immunology; Skin Neoplasms - pathology; Th17 Cells - drug effects; Th17 Cells - immunology; Th17 Cells - metabolism; Tomography, X-Ray Computed; Treatment Outcome; pembrolizumab; melanoma; sarcoidosis; programmed cell death 1; nivolumab
• ISSN: 1756-1841; 1756-185X
• DOI: 10.1111/1756-185X.13076

Aim Sarcoidosis is a multisystem granulomatous disease. This condition has a documented association with the diagnosis of melanoma and can be induced in melanoma patients receiving anti‐neoplastic therapy. We evaluated a case series of melanoma patients who developed immunotherapy‐induced sarcoidosis. Methods Three patients with melanoma (n = 1 resected Stage III, n = 2 metastatic) treated with anti‐programmed cell death (PD)‐1 antibody therapy at two institutions developed biopsy‐proven sarcoidosis. We used mass cytometry to determine expression of the relevant chemokine receptors (CR) by peripheral blood mononuclear cells for two of the three patients who developed sarcoidosis and 13 melanoma patients who did not. Blood samples were collected before receiving PD‐1 checkpoint inhibitor therapy. Results Immunophenotypic analysis demonstrated abnormally high numbers of circulating Th17.1 (CCR6+CCR4−CXCR3+CCR10−) cells prior to commencing PD‐1 checkpoint inhibitor therapy in five of 15 melanoma patients, including both the patients who developed sarcoidosis during the course of therapy. Conclusion Our findings support prior literature implicating Th17.1 cells in the pathogenesis of sarcoidosis. However, we demonstrate these findings in patients with melanoma prior to administration of checkpoint therapy and before the onset of clinically symptomatic sarcoidosis. The identification of elevated Th17.1 cells in melanoma patients who have not developed sarcoidosis may reflect the established association between melanoma and sarcoidosis. With some patients receiving these agents over a prolonged period, the clinical course of immunotherapy‐induced sarcoidosis is uncertain.